. During the last three decades there has been a dramatic increase in the frequency of fungal infections in immunodeficient hosts. Species of Cryptococcus, Candida, Aspergillus and Pneumocystis carinii are important opportunistic causative agents, while species of Coccidioides, Histoplasma and Sporothrix are important primary pathogens. Treatment of fungal infections is limited to a few options including amphotericin B and azoles. Unfortunately, amphotericin B is toxic and clinical resistance to azoles is increasing. These observations underscore the need for new antifungals. Permatins are small proteins found in seeds of plants and have homology to thaumatin and Group 5 pathogenesis-related proteins. Zeamatin, the type family member from corn, has potent in vitro fungicidal activity against human pathogenic fungi. In this Phase I SBIR the PI proposes to test the feasibility of zeamatin as an antifungal therapeutic in humans in three specific aims. Aim One: purify zeamatin under cGMP conditions from hi- lysine cornmeal. Aim Two: Test purified zeamatin in an in vivo vaginal candidiasis murine model. Aim three: Test purified zeamatin in an in vivo systemic candidiasis murine model. These results will determine whether zeamatin has antifungal activity in vivo and will be an important step in the development of zeamatin as a therapeutic for use in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE